Proline, glutamic acid and leucine-rich protein 1 (PELP1)

Proline, glutamic acid and leucine-rich protein 1 (PELP1) is a versatile scaffold protein and a key coactivator for several nuclear receptors, including the estrogen receptor (ER) and androgen receptor (AR). It facilitates both genomic actions within the nucleus and rapid non-genomic signaling in the cytoplasm by interacting with various kinases such as Src, PI3K, and MAPK (UniProt Q8IZL8; PubMed: 25635324). PELP1 also plays a significant role in ribosome biogenesis and chromatin remodeling, contributing to its essential nature in cellular growth and division (PubMed: 21724585). In the context of human disease, PELP1 is frequently overexpressed in hormone-responsive cancers like breast, ovarian, and prostate cancers, where it is associated with poor prognosis, metastasis, and the development of resistance to standard endocrine therapies (PubMed: 30104309). Targeting PELP1 is an emerging strategy in oncology, with experimental agents like the small molecule ERX-11 showing efficacy in preclinical models by specifically disrupting the PELP1-ER interaction (PubMed: 28794128). Its status as a master regulator of multiple oncogenic pathways makes it a high-value target for overcoming therapy resistance in advanced malignancies.

Other names

Modulator of nongenomic activity of estrogen receptorMNARTranscription factor HREP160

Inhibition of the interaction between PELP1 and nuclear receptors (such as the estrogen receptor) to block both genomic and non-genomic oncogenic signaling.